Exposure of pregnant monkeys to the widely-used chemical bisphenol A (BPA) disrupts development of fetal ovaries, potentially causing birth defects and reproductive problems that would not emerge for a generation, according to research by Dr. Patricia Hunt and colleagues at Washington State University and Dr. Catherine VandeVoort at the CNPRC. The research was reported in a paper published this week (Sept. 24) in the journal Proceedings of the National Academy of Sciences.

(A news release from Washington State University can be found here.)

BPA is a chemical used in plastics, epoxy resins that line cans, and cash register receipts. Most people in the United States have measurable levels of BPA in their blood that indicate that exposure is nearly continuous. By using an animal with a reproductive system like that of humans, the research bolsters earlier work by Hunt and others documenting widespread reproductive effects in rodents.

What was done in this study?
Pregnant monkeys were given doses of BPA designed to produce a blood level of BPA similar to that found in humans. In this paper, the researchers looked at effects on the developing ovaries of female fetuses.This study has also provided samples to investigators working on other organ systems. A study on the mammary gland was led by researchers at Tufts and published in PNAS in May. Additional papers describing effects on other organs should be finished soon.

What were the findings?
When BPA was given in the second trimester of pregnancy, the fetal eggs had an increased incidence of chromosome damage. This damage could lead to miscarriage or birth defects in future offspring of the fetus. When given later in pregnancy, BPA disrupted the packaging of eggs into follicles. Follicles are the structures that eggs need to develop and grow properly.

“The effect of BPA on development of the ovary is especially concerning because the dose that is given to the pregnant female affects the fetus and if that fetus is female then the eggs that are being formed in the developing ovary are affected,” VandeVoort said. “The final results of the exposure may not been seen until the fetus grows up and has offspring of its own. If these same changes were happening in people, then the effects of BPA exposure in a pregnant woman might not been seen for 20 or 30 or more years, when her child reaches adulthood and has children of her own.”

“We are very concerned about the consequences of large numbers of eggs not forming proper follicles. All the eggs a female will ever have are formed before birth. The effect we have seen in this study could mean a shortened reproductive lifespan.”

Why use a monkey model?
Low doses of BPA have been shown to disrupt development in rodent models, but because mice naturally have low estrogen levels they may be more sensitive to BPA than humans. The study of BPA in a primate model is critical because the rhesus monkey has estrogen levels as well as reproductive and developmental processes that are similar to humans. The amount of BPA given to the monkeys in the study produced blood levels of BPA that are slightly lower than the mean level measured in humans in recent studies. Therefore, the results of this study are highly relevant to human health.

One of the major objectives of the CNPRC is to conduct primate studies in critical areas where rodent experiments are not sufficient. This study will help inform the public and regulatory agencies of the potential effects of BPA in humans.

“It’s important to do studies in a model with estrogen levels similar to those in women,” VandeVoort said. “Fetal development is very different in rodents and primates.”